Early versus Later Anticoagulation for Stroke with Atrial Fibrillation
Authors: Urs Fischer, Masatoshi Koga, Daniel Strbian, Mattia Branca, Stefanie Abend, Sven Trelle, Maurizio Paciaroni, Götz Thomalla, Patrik Michel, Krassen Nedeltchev, Leo H. Bonati, George Ntaios, Thomas Gattringer, Else-Charlotte Sandset, Peter Kelly, Robin Lemmens, P.N. Sylaja, Diana Aguiar de Sousa, Natan M. Bornstein, Zuzana Gdovinova, Takeshi Yoshimoto, Marjaana Tiainen, Helen Thomas, Manju Krishnan, Gek C. Shim, Christoph Gumbinger, Jochen Vehoff, Liqun Zhang, Kosuke Matsuzono, Espen Kristoffersen, Philippe Desfontaines, Peter Vanacker, Angelika Alonso, Yusuke Yakushiji, Caterina Kulyk, Dimitri Hemelsoet, Sven Poli, Ana Paiva Nunes, Nicoletta Caracciolo, Peter Slade, Jelle Demeestere, Alexander Salerno, Markus Kneihsl, Timo Kahles, Daria Giudici, Kanta Tanaka, Silja Räty, Rea Hidalgo, David J. Werring, Martina Göldlin, Marcel Arnold, Cecilia Ferrari, Seraina Beyeler, Christian Fung, Bruno J. Weder, Turgut Tatlisumak, Sabine Fenzl, Beata Rezny-Kasprzak, Arsany Hakim, Georgia Salanti, Claudio Bassetti, Jan Gralla, David J. Seiffge, Thomas Horvath, Jesse Dawson
Journal: New England Journal of Medicine (2023)

The effect of early as compared with later initiation of direct oral anticoagulants (DOACs) in persons with atrial fibrillation who have had an acute ischemic stroke is unclear.We performed an investigator-initiated, open-label trial at 103 sites in 15 countries. Participants were randomly assigned in a 1:1 ratio to early anticoagulation (within 48 hours after a minor or moderate stroke or on day 6 or 7 after a major stroke) or later anticoagulation (day 3 or 4 after a minor stroke, day 6 or 7 after a moderate stroke, or day 12, 13, or 14 after a major stroke). Assessors were unaware of the trial-group assignments. The primary outcome was a composite of recurrent ischemic stroke, systemic embolism, major extracranial bleeding, symptomatic intracranial hemorrhage, or vascular death within 30 days after randomization. Secondary outcomes included the components of the composite primary outcome at 30 and 90 days.Of 2013 participants (37% with minor stroke, 40% with moderate stroke, and 23% with major stroke), 1006 were assigned to early anticoagulation and 1007 to later anticoagulation. A primary-outcome event occurred in 29 participants (2.9%) in the early-treatment group and 41 participants (4.1%) in the later-treatment group (risk difference, -1.18 percentage points; 95% confidence interval [CI], -2.84 to 0.47) by 30 days. Recurrent ischemic stroke occurred in 14 participants (1.4%) in the early-treatment group and 25 participants (2.5%) in the later-treatment group (odds ratio, 0.57; 95% CI, 0.29 to 1.07) by 30 days and in 18 participants (1.9%) and 30 participants (3.1%), respectively, by 90 days (odds ratio, 0.60; 95% CI, 0.33 to 1.06). Symptomatic intracranial hemorrhage occurred in 2 participants (0.2%) in both groups by 30 days.In this trial, the incidence of recurrent ischemic stroke, systemic embolism, major extracranial bleeding, symptomatic intracranial hemorrhage, or vascular death at 30 days was estimated to range from 2.8 percentage points lower to 0.5 percentage points higher (based on the 95% confidence interval) with early than with later use of DOACs. (Funded by the Swiss National Science Foundation and others; ELAN ClinicalTrials.gov number, NCT03148457.).